PMID- 25517305
OWN - NLM
STAT- MEDLINE
DCOM- 20150824
LR  - 20211203
IS  - 1942-0870 (Electronic)
IS  - 1942-0862 (Print)
IS  - 1942-0862 (Linking)
VI  - 6
IP  - 5
DP  - 2014
TI  - Monomeric IgG1 Fc molecules displaying unique Fc receptor interactions that are 
      exploitable to treat inflammation-mediated diseases.
PG  - 1201-10
LID - 10.4161/mabs.29835 [doi]
AB  - The IgG1 Fc is a dimeric protein that mediates important antibody effector 
      functions by interacting with Fcgamma receptors (FcgammaRs) and the neonatal Fc receptor 
      (FcRn). Here, we report the discovery of a monomeric IgG1 Fc (mFc) that bound to 
      FcgammaRI with very high affinity, but not to FcgammaRIIIa, in contrast to wild-type 
      (dimeric) Fc. The binding of mFc to FcRn was the same as that of dimeric Fc. To 
      test whether the high-affinity binding to FcgammaRI can be used for targeting of 
      toxins, a fusion protein of mFc with a 38 kDa Pseudomonas exotoxin A fragment 
      (PE38), was generated. This fusion protein killed FcgammaRI-positive macrophage-like 
      U937 cells but not FcgammaRI-negative cells, and mFc or PE38 alone had no killing 
      activity. The lack of binding to FcgammaRIIIa resulted in the absence of Fc-mediated 
      cytotoxicity of a scFv-mFc fusion protein targeting mesothelin. The 
      pharmacokinetics of mFc in mice was very similar to that of dimeric Fc. The mFc's 
      unique FcgammaRs binding pattern and related functionality, combined with its small 
      size, monovalency and the preservation of FcRn binding which results in 
      relatively long half-life in vivo, suggests that mFc has great potential as a 
      component of therapeutics targeting inflammation mediated by activated 
      macrophages overexpressing FcgammaRI and related diseases, including cancer.
FAU - Ying, Tianlei
AU  - Ying T
AD  - a Key Laboratory of Medical Molecular Virology of Ministries of Education and 
      Health; Shanghai Medical College ; Fudan University ; Shanghai , China.
FAU - Feng, Yang
AU  - Feng Y
FAU - Wang, Yanping
AU  - Wang Y
FAU - Chen, Weizao
AU  - Chen W
FAU - Dimitrov, Dimiter S
AU  - Dimitrov DS
LA  - eng
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PL  - United States
TA  - MAbs
JT  - mAbs
JID - 101479829
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immunoconjugates)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Msln protein, mouse)
RN  - 0 (Receptors, Fc)
RN  - 0 (pseudomonas exoprotein A protein, Pseudomonas aeruginosa)
RN  - J27WDC343N (Mesothelin)
RN  - TW3XAW0RCY (Fc receptor, neonatal)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Monoclonal/immunology/metabolism/pharmacokinetics
MH  - Antibody-Dependent Cell Cytotoxicity/drug effects
MH  - Bacterial Proteins/chemistry/pharmacology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Flow Cytometry
MH  - HEK293 Cells
MH  - Histocompatibility Antigens Class I/immunology/metabolism
MH  - Humans
MH  - Immunoconjugates/chemistry/pharmacology
MH  - Immunoglobulin Fc Fragments/chemistry/genetics/*immunology
MH  - Immunoglobulin G/*immunology/metabolism/pharmacology
MH  - Inflammation/drug therapy/*immunology/metabolism
MH  - Mesothelin
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Protein Binding/immunology
MH  - Receptors, Fc/*immunology/metabolism
MH  - Sequence Homology, Amino Acid
MH  - U937 Cells
PMC - PMC4622432
OTO - NOTNLM
OT  - ADCC
OT  - FcRn
OT  - Fcgamma receptors
OT  - chronic inflammation
OT  - monomeric Fc
EDAT- 2014/12/18 06:00
MHDA- 2015/08/25 06:00
PMCR- 2015/10/30
CRDT- 2014/12/18 06:00
PHST- 2014/12/18 06:00 [entrez]
PHST- 2014/12/18 06:00 [pubmed]
PHST- 2015/08/25 06:00 [medline]
PHST- 2015/10/30 00:00 [pmc-release]
AID - 972751 [pii]
AID - 10.4161/mabs.29835 [doi]
PST - ppublish
SO  - MAbs. 2014;6(5):1201-10. doi: 10.4161/mabs.29835.